Plasma Proprotein Convertase Subtilisin Kexin Type 9 as a Predictor of Carotid Atherosclerosis in Asymptomatic Adults

Heart Lung Circ. 2016 May;25(5):520-5. doi: 10.1016/j.hlc.2015.10.017. Epub 2015 Nov 18.

Abstract

Background: Atherosclerosis is a lipid-driven inflammatory disease of the arterial wall involving complex and multifactorial processes. Proprotein convertase subtilisin kexin type 9 (PCSK9) may play a role in the development of atherosclerosis.

Methods: We investigated the associations between serum PCSK9 and carotid intima-medial wall thickness (IMT), a measure of subclinical atherosclerosis that predicts cardiovascular events, in 295 asymptomatic subjects from community. Carotid IMT was determined by high-resolution B-mode carotid ultrasonography and serum PCSK9 was measured by immunoassay.

Results: In univariate analysis, serum PCSK9 concentration was positively (P<0.05 in all) associated with age (r=0.204), BMI (r=0.149), waist circumference (r=0.139), systolic blood pressures (r=0.116), glucose (r=0.211), insulin (r=0.178), HOMA score (r=0.195), plasma triglyceride (r=0.285), total cholesterol (r=0.241) and LDL-cholesterol concentrations (r=0.172). In multivariate regression including male gender, hypertension, smoking status, HOMA score, obesity, LDL-cholesterol, lipoprotein (a) or markers of inflammation, serum PCSK9 remained an independent predictor of mean carotid IMT (P<0.001).

Conclusions: These data suggest that serum levels of PCSK9 may contribute to increased risk of subclinical carotid atherosclerosis independent of conventional risk factors. Whether PCSK9 inhibition improves cardiovascular outcomes remains to be demonstrated in large, ongoing clinical trials.

Keywords: Carotid IMT and Cardiovascular disease; PCSK9.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carotid Artery Diseases* / blood
  • Carotid Artery Diseases* / diagnostic imaging
  • Carotid Intima-Media Thickness*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Proprotein Convertase 9 / blood*
  • Risk Factors
  • Sex Factors

Substances

  • PCSK9 protein, human
  • Proprotein Convertase 9